Docetaxel/Cyclophosphamide Improves Survival Over AC in Early Breast Cancer

December 13, 2007

Compared with standard treatment with doxorubicin/cyclophosphamide (AC), four cycles of docetaxel (Taxotere) plus cyclophosphamide (TC) improved both disease-free and overall survival in the extended follow-up and analysis of US Oncology Adjuvant Trial 9735.

Compared with standard treatment with doxorubicin/cyclophosphamide (AC), four cycles of docetaxel (Taxotere) plus cyclophosphamide (TC) improved both disease-free and overall survival in the extended follow-up and analysis of US Oncology Adjuvant Trial 9735.

Stephen Jones
Photo Courtesy © SABCS/Todd Buchanan 2007

At SABCS 2005, US Oncology investigators reported the 5-year results of a randomized trial of four cycles of TC compared with four cycles of AC in 1016 women with node-negative and node-positive early breast cancer. While a significant improvement in disease-free survival was demonstrated with TC, overall survival was similar between the arms. Now, with a median of 7 years follow-up, a survival benefit has also been shown for the TC regimen, said Stephen Jones, MD, medical director of US Oncology Research in Houston. "TC is a highly effective, modestly toxic, nonanthracycline adjuvant chemotherapy regimen. With longer follow-up, it has stood the test of time and now shows a survival advantage. TC should be considered a standard regimen for early breast cancer," Dr. Jones said. Patients with stage I, II, or operable stage III invasive breast cancer were randomized to four cycles every 21 days of doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 or to docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2. The study excluded patients who had received neoadjuvant chemotherapy and those with tumors >7 cm or <1 cm. The current analysis was based on a median follow-up of 7 years. Disease-free survival was 81% for the TC arm and 76% for the AC arm, for a relative risk reduction of 26% favoring TC (P = .03). Overall survival was 87% for TC and 82% for AC, for a 31% relative risk reduction at 7 years (P = .03), Dr. Jones said. Regardless of age (<65 or ≥65) TC improved disease-free and overall survival as compared with AC. The worst outcomes were observed in patients ≥65 receiving AC. Furthermore, TC was efficacious in patients with HER2-positive tumors as well as HER2-negative disease, though this was based on a limited sample of patients. Disease-free survival risk was reduced by 44% in HER2-negative patients and by 27% in HER2-positive patients, he said. TC was well tolerated in both age groups. In the older patients, TC was associated with slightly more febrile neutropenia but with less anemia than AC and with less long-term toxicity (cardiac and bone marrow). Dr. Jones indicated that he would be "comfortable" recommending TC for node-negative patients or those with one to three positive nodes, but he might still prefer the anthracycline-based regimen in patients at higher risk, ie, those with locally advanced disease or with four or more positive nodes. US Oncology is now involved in a new study that will further evaluate the need for anthracyclines by comparing six cycles of TC to six cycles of TAC (docetaxel/doxorubicin/cyclophosphamide), he said.

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.